title: TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants.
abstract: While numerous life-extending manipulations have been discovered in the nematode Caenorhabditis elegans, one that remains most enigmatic is disruption of oxidative phosphorylation. In order to unravel how such an ostensibly deleterious manipulation can extend lifespan, we sought to identify the ensemble of nuclear transcription factors that are activated in response to defective mitochondrial electron transport chain (ETC) function. Using a feeding RNAi approach, we targeted over 400 transcription factors and identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors--AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4--were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF-1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.
authors.affiliation: Barshop Institute for Longevity and Aging Studies and Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.
authors.forename: Maruf H
authors.initials: MH
authors.lastname: Khan
authors.forename: Melissa
authors.initials: M
authors.lastname: Ligon
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Hussey
authors.forename: Bryce
authors.initials: B
authors.lastname: Hufnal
authors.forename: Robert
authors.initials: R
authors.lastname: Farber
authors.forename: Erin
authors.initials: E
authors.lastname: Munkácsy
authors.forename: Amanda
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Andy
authors.initials: A
authors.lastname: Dillow
authors.forename: Erynn
authors.initials: E
authors.lastname: Kahlig
authors.forename: Shane L
authors.initials: SL
authors.lastname: Rea
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000502:physiology*; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D013836:Thiamin Pyrophosphokinase / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C541178:HIF-1 protein, C elegans; C532582:TAF-4 protein, C elegans; D014157:Transcription Factors; C443102:Isp-1 protein, Caenorhabditis elegans; D013836:Thiamin Pyrophosphokinase; D014450:Electron Transport Complex III